The measurement of glomerular filtration rate (GFR) is an important index in the evaluation and follow-up of patients with renal disease and transplant recipients. Rigorous assessment of the glomerular filtration rate has been accomplished by measurement of the renal clearance of inulin, a fructose polymer that fulfills the criteria for a filtration marker. See M. Price, J. Urol., 107, 339 (1972). However, the classical inulin clearance method is not suitable for routine clinical purposes, since it requires continuous infusion and, sometimes, bladder catheterization of the patients. H. W. Smith, in The Kidney: Structure and Function in Health and Disease, H. W. Smith, ed., Oxford University Press, NY (1951) at pages 39-62.
More precise evaluation of renal function has been determined by infusion of .sup.51 Cr-EDTA and .sup.125 I-iothalamate. However, radioactive exposure, appropriate handling, disposal of radioactive materials, and cost (in part related to deterioration and limited shelf life of radioisotopes) has limited the use of radioisotopes. See, J. Brochner-Mortensen et al., Scand. J. Clin. Lab. Invest., 23, 301 (1969); G. Bajaj et al., Pediatr. Nephrol., 10, 25 (1996); and A. H. Israelit et al., Kid. Int., 4, 346 (1973).
Attempts to avoid exposure to radioisotopes have led to the investigation of new techniques for measuring GFR, and several methods have been developed for measurement of iothalamate using HPLC determinations. See, for example, A. Al-Uzri et al., Kid. Int., 41, 1701 (1992); T. Prueksaritanont et al., J. Chrom., 306, 89 (1984); M. A. Holliday et al., Kid. Int., 41, 1701 (1992). These methods avoid radioisotopes but are labor intensive. Therefore, they are not widely accepted for routine use.
Other methods have focused on x-ray fluorescence of iohexol for measurement of serum concentration and estimated plasma clearance with a one or two blood sample technique. The iohexol technology using the Renalyzer avoids radioisotope problems but is less sensitive, requiring relatively large doses of the injected drug in order to measure GFR. See, for example, S. C. W. Brown et al., J. Urol., 146, 675 (1991).
Rocco et al., Am. J. Nephrol., 16, 138 (1996), recognized the advantage of HPLC for measuring iohexol in order to use relatively smaller sample volumes. This method, however, is labor intensive and time consuming. Because of the perceived limitations of both the x-ray fluorescence and HPLC, Rocco et al., Am. J. Kid. Dis., 28, 173 (1996), investigated the applicability of capillary electrophoresis (CE) for the determination of serum iohexol. They reported utilization of capillary electrophoresis using a relatively large (5 ml) dose of injected iohexol to evaluate a monoexponential disappearance curve for determination of GFR in patients. Clearances using this method were compared with the "standard" clearance of .sup.125 I-iothalamate and iohexol measured by an HPLC method.
However, a continuing need exists for simple methods to accurately measure GFR using non-radioactive tracers in small doses.